Author/Authors :
Hitosugi، نويسنده , , Taro and Zhou، نويسنده , , Lu and Elf، نويسنده , , Shannon and Fan، نويسنده , , Jun and Kang، نويسنده , , Hee-Bum and Seo، نويسنده , , Jae Ho and Shan، نويسنده , , Changliang and Dai، نويسنده , , Qing and Zhang، نويسنده , , Liang-Liang Xie، نويسنده , , Jianxin and Gu، نويسنده , , Ting-Lei and Jin، نويسنده , , Peng and Ale?kovi?، نويسنده , , Masa and LeRoy، نويسنده , , Gary Chih-Kang Liu، نويسنده , , Yibin and Sudderth، نويسنده , , Jessica A. and DeBerardinis، نويسنده , , Ralph J. and Luan، نويسنده , , Chi-Hao and Chen، نويسنده , , Georgia Z. and Muller، نويسنده , , Susan and Shin، نويسنده , , Dong M. and Owonikoko، نويسنده , , Taofeek K. and Lonial، نويسنده , , Sagar and Arellano، نويسنده , , Martha L. and Khoury، نويسنده , , Hanna J. and Khuri، نويسنده , , Fadlo R. and Lee، نويسنده , , Benjamin H. and Ye، نويسنده , , Keqiang and Boggon، نويسنده , , Titus J. and Kang، نويسنده , , Sumin and He، نويسنده , , Chuan and Chen، نويسنده , , Jing، نويسنده ,
Abstract :
Summary
unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.
